M2型小胶质细胞极化促进少突胶质祖细胞途的分化———促进多发性硬化症髓鞘再生的有效途径
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中国中医科学院 中药研究所,北京 100700

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R-33


M2 microglia promote oligodendrocyte precursor cell differentiation: an effective therapy for stimulating remyelination in multiple sclerosis
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China Academy of Chinese Medical Sciences Institute of Chinese Materia Medica, Beijng 100700,China

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    摘要:

    中枢神经系统(central nervous system, CNS)持续性的自身免疫性炎症和髓鞘脱失是多发性硬化症 (multiple sclerosis, MS)的典型病理特征,尤其以神经系统持续衰退导致慢性脱髓鞘轴突病变引起的继发-进展型 MS(secondary progressive multiple sclerosis, SPMS)最为难治。 有多种免疫细胞和神经细胞参与 MS 的疾病进程,但在 CNS 中主要负责炎症反应调 节和髓鞘再生的分别为小胶质细胞 ( microglia, MG) 和少突胶质祖细胞 ( oligodendrocyte precursor cells, OPCs)。 在 MS 患者病灶部位发现具有 MG M1 / M2 极化失衡和 OPCs 分化受阻导致的髓鞘再生障碍的现象,以往研究通常把 MG 的极化失衡和 OPCs 分化受阻当成两个独立的现象。 但近期研究表明,两者之间存在交互式作用,MG 极化失衡是导致 OPCs 分化受阻的核心机制之一,而 OPCs 也可反作用于 MG,两者共同影响髓鞘的再生过程。 在 MS 的治疗上,目前临床上治疗 MS 的药物只能对症治疗,无法根治 MS。 探索新的药物研发方向是目前 MS 临床治疗中亟待解决的关键科学问题。 本研究就“从极化到分化”这一领域进行综述, 聚焦于通过靶向 MG 极化失衡从而促进 OPCs 的分化和髓鞘再生的新策略,以期为 MS 及其他以 CNS 组织修复障 碍为共同病理特征的神经退行性疾病的治疗提供新的药物研发方向。

    Abstract:

    Demyelination and autoimmune chronic inflammation in the central nervous system are the typical pathological features of multiple sclerosis (MS). A range of immune and nerve cells participate in the disease process of MS. The regulation of inflammation and remyelination is mainly performed by microglia ( MG) and oligodendrocyte precursor cells (OPCs), respectively. In non-repairing lesions of MS patients, an imbalance of MG polarization and a failure of OPC differentiation are likely to contribute to inefficient remyelination. Previous researchers have emphasized that these are independent functions. However, it has recently been reported that MG polarization is closely connected with OPC differentiation, an imbalance of MG polarization can inhibit OPC differentiation. Conversely, OPCs can also interfere with the inflammatory response of MG. Taken together, interactions between MG and OPCs form a holistic entity and function as a crucial mechanism of remyelination. Currently approved treatments for MS mainly target the aberrant immune response, and are able to improve the disease-related symptoms but do not cure MS, particularly intractable secondary progressive multiple sclerosis ( SPMS ). Therapeutic strategies or agents that promote remyelination remain under extensive investigation. This review summarizes the interactions between MG polarization and OPC differentiation, and provides strategies to overcome the failure of OPC differentiation by attempting to rebalance MG polarization, which will be beneficial for the development of demyelinating diseases including SPMS.

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刘 丽,李 琦,杜欣珂,冉庆森,孙立东,杨 庆,李玉洁,陈 颖,王娅杰,翁小刚,蔡维艳,朱晓新. M2型小胶质细胞极化促进少突胶质祖细胞途的分化———促进多发性硬化症髓鞘再生的有效途径[J].中国比较医学杂志,2022,32(2):126~132.

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  • 收稿日期:2020-11-09
  • 在线发布日期: 2022-04-12
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